In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands
The synthesis and in vitro anticancer activity of dihalo(η6-p-cymene)(3,5,6-bicyclophosphite-α-D-glucofuranoside)ruthenium(II) complexes are described. The compds. were characterized by NMR spectroscopy and ESI mass spectrometry, and the mol. structures of dichlorido-, dibromido- and diiodido(η6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-α-D-glucofuranoside)ruthenium(II) were detd. by X- ray diffraction anal. The complexes were shown to undergo aquation of the first halido ligand in aq. soln., followed by hydrolysis of a P-O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calcns. The aquation of the complexes was markedly suppressed in 100 mM NaCl soln., and notably only very slow hydrolysis of the P-O bond was obsd. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-α-D-glucofuranoside complex is the most cytotoxic compd. in human cancer cell lines (IC50 values from 30 to 300 μM depending on the cell line).